Urinary dopamine as a potential index of the transport activity of multidrug and toxin extrusion in the kidney

Moto Kajiwara, Tsuyoshi Ban, Kazuo Matsubara, Yoichi Nakanishi, Satohiro Masuda

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

Dopamine is a cationic natriuretic catecholamine synthesized in proximal tubular cells (PTCs) of the kidney before secretion into the lumen, a key site of its action. However, the molecular mechanisms underlying dopamine secretion into the lumen remain unclear. Multidrug and toxin extrusion (MATE) is a H+/organic cation antiporter that is highly expressed in the brush border membrane of PTCs and mediates the efflux of organic cations, including metformin and cisplatin, from the epithelial cells into the urine. Therefore, we hypothesized that MATE mediates dopamine secretion, a cationic catecholamine, into the tubule lumen, thereby regulating natriuresis. Here, we show that [3H]dopamine uptake in human (h) MATE1-, hMATE-2K- and mouse (m) MATE-expressing cells exhibited saturable kinetics. Fluid retention and decreased urinary excretion of dopamine and Na+ were observed in Mate1-knockout mice compared to that in wild-type mice. Imatinib, a MATE inhibitor, inhibited [3H]dopamine uptake by hMATE1-, hMATE2-K- and mMATE1-expressing cells in a concentration-dependent manner. At clinically-relevant concentrations, imatinib inhibited [3H]dopamine uptake by hMATE1- and hMATE2-K-expressing cells. The urinary excretion of dopamine and Na+ decreased and fluid retention occurred in imatinib-treated mice. In conclusion, MATE transporters secrete renally-synthesized dopamine, and therefore, urinary dopamine has the potential to be an index of the MATE transporter activity.

元の言語英語
記事番号1228
ジャーナルInternational journal of molecular sciences
17
発行部数8
DOI
出版物ステータス出版済み - 8 2016

Fingerprint

dopamine
kidneys
Extrusion
Dopamine
Kidney
secretions
lumens
catecholamine
mice
transporter
cells
excretion
Catecholamines
Cations
knockout mice
Positive ions
Antiporters
efflux
cations
Natriuresis

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

これを引用

Urinary dopamine as a potential index of the transport activity of multidrug and toxin extrusion in the kidney. / Kajiwara, Moto; Ban, Tsuyoshi; Matsubara, Kazuo; Nakanishi, Yoichi; Masuda, Satohiro.

:: International journal of molecular sciences, 巻 17, 番号 8, 1228, 08.2016.

研究成果: ジャーナルへの寄稿記事

Kajiwara, Moto ; Ban, Tsuyoshi ; Matsubara, Kazuo ; Nakanishi, Yoichi ; Masuda, Satohiro. / Urinary dopamine as a potential index of the transport activity of multidrug and toxin extrusion in the kidney. :: International journal of molecular sciences. 2016 ; 巻 17, 番号 8.
@article{bcd466287dc14c0da4ccfecf7969f50a,
title = "Urinary dopamine as a potential index of the transport activity of multidrug and toxin extrusion in the kidney",
abstract = "Dopamine is a cationic natriuretic catecholamine synthesized in proximal tubular cells (PTCs) of the kidney before secretion into the lumen, a key site of its action. However, the molecular mechanisms underlying dopamine secretion into the lumen remain unclear. Multidrug and toxin extrusion (MATE) is a H+/organic cation antiporter that is highly expressed in the brush border membrane of PTCs and mediates the efflux of organic cations, including metformin and cisplatin, from the epithelial cells into the urine. Therefore, we hypothesized that MATE mediates dopamine secretion, a cationic catecholamine, into the tubule lumen, thereby regulating natriuresis. Here, we show that [3H]dopamine uptake in human (h) MATE1-, hMATE-2K- and mouse (m) MATE-expressing cells exhibited saturable kinetics. Fluid retention and decreased urinary excretion of dopamine and Na+ were observed in Mate1-knockout mice compared to that in wild-type mice. Imatinib, a MATE inhibitor, inhibited [3H]dopamine uptake by hMATE1-, hMATE2-K- and mMATE1-expressing cells in a concentration-dependent manner. At clinically-relevant concentrations, imatinib inhibited [3H]dopamine uptake by hMATE1- and hMATE2-K-expressing cells. The urinary excretion of dopamine and Na+ decreased and fluid retention occurred in imatinib-treated mice. In conclusion, MATE transporters secrete renally-synthesized dopamine, and therefore, urinary dopamine has the potential to be an index of the MATE transporter activity.",
author = "Moto Kajiwara and Tsuyoshi Ban and Kazuo Matsubara and Yoichi Nakanishi and Satohiro Masuda",
year = "2016",
month = "8",
doi = "10.3390/ijms17081228",
language = "English",
volume = "17",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

TY - JOUR

T1 - Urinary dopamine as a potential index of the transport activity of multidrug and toxin extrusion in the kidney

AU - Kajiwara, Moto

AU - Ban, Tsuyoshi

AU - Matsubara, Kazuo

AU - Nakanishi, Yoichi

AU - Masuda, Satohiro

PY - 2016/8

Y1 - 2016/8

N2 - Dopamine is a cationic natriuretic catecholamine synthesized in proximal tubular cells (PTCs) of the kidney before secretion into the lumen, a key site of its action. However, the molecular mechanisms underlying dopamine secretion into the lumen remain unclear. Multidrug and toxin extrusion (MATE) is a H+/organic cation antiporter that is highly expressed in the brush border membrane of PTCs and mediates the efflux of organic cations, including metformin and cisplatin, from the epithelial cells into the urine. Therefore, we hypothesized that MATE mediates dopamine secretion, a cationic catecholamine, into the tubule lumen, thereby regulating natriuresis. Here, we show that [3H]dopamine uptake in human (h) MATE1-, hMATE-2K- and mouse (m) MATE-expressing cells exhibited saturable kinetics. Fluid retention and decreased urinary excretion of dopamine and Na+ were observed in Mate1-knockout mice compared to that in wild-type mice. Imatinib, a MATE inhibitor, inhibited [3H]dopamine uptake by hMATE1-, hMATE2-K- and mMATE1-expressing cells in a concentration-dependent manner. At clinically-relevant concentrations, imatinib inhibited [3H]dopamine uptake by hMATE1- and hMATE2-K-expressing cells. The urinary excretion of dopamine and Na+ decreased and fluid retention occurred in imatinib-treated mice. In conclusion, MATE transporters secrete renally-synthesized dopamine, and therefore, urinary dopamine has the potential to be an index of the MATE transporter activity.

AB - Dopamine is a cationic natriuretic catecholamine synthesized in proximal tubular cells (PTCs) of the kidney before secretion into the lumen, a key site of its action. However, the molecular mechanisms underlying dopamine secretion into the lumen remain unclear. Multidrug and toxin extrusion (MATE) is a H+/organic cation antiporter that is highly expressed in the brush border membrane of PTCs and mediates the efflux of organic cations, including metformin and cisplatin, from the epithelial cells into the urine. Therefore, we hypothesized that MATE mediates dopamine secretion, a cationic catecholamine, into the tubule lumen, thereby regulating natriuresis. Here, we show that [3H]dopamine uptake in human (h) MATE1-, hMATE-2K- and mouse (m) MATE-expressing cells exhibited saturable kinetics. Fluid retention and decreased urinary excretion of dopamine and Na+ were observed in Mate1-knockout mice compared to that in wild-type mice. Imatinib, a MATE inhibitor, inhibited [3H]dopamine uptake by hMATE1-, hMATE2-K- and mMATE1-expressing cells in a concentration-dependent manner. At clinically-relevant concentrations, imatinib inhibited [3H]dopamine uptake by hMATE1- and hMATE2-K-expressing cells. The urinary excretion of dopamine and Na+ decreased and fluid retention occurred in imatinib-treated mice. In conclusion, MATE transporters secrete renally-synthesized dopamine, and therefore, urinary dopamine has the potential to be an index of the MATE transporter activity.

UR - http://www.scopus.com/inward/record.url?scp=84980319936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84980319936&partnerID=8YFLogxK

U2 - 10.3390/ijms17081228

DO - 10.3390/ijms17081228

M3 - Article

C2 - 27483254

AN - SCOPUS:84980319936

VL - 17

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 8

M1 - 1228

ER -